Pharmaceutical formulations which contain budesonide and are for oral administration with controlled release in the intestinal tract are known from EP-A-0 720 473.
These formulations have been used for a relatively long time in the treatment of intestinal diseases, such as Crohn's disease, are effective (Bar-Meir, Gastroenterology, 1998, p. 835-840) and have an improved safety profile (Andus, Digestive Diseases and Sciences, 1 Feb. 2003, p. 373-378).
The use of glucocorticoids, in particular budesonide, is generally known for the treatment of diseases which are associated with inflammation processes. These diseases also include those of the oral cavity, the pharynx and the oesophagus. The active ingredient budesonide has been used successfully, for example in GVHD (graft versus host disease) (Elad et al., Oral Surg. Oral Med. Oral Pathol. and Radial Endod. 2003, 95, p. 308-311).
WO03/06629 describes lozenges containing an active ingredient core which is sheathed by a water-soluble polysaccharide (gellan gum). The active ingredient is inside the core and not intermixed with the sheath. Glucocorticoids, for example budesonide are mentioned as possible active ingredients. The tablet is suitable for buccal use.
For treating inflammatory processes in the oral cavity, the preparation of a drug form is desired which is reproducible as a ready-for-use formulation, releases sufficiently high concentrations of active ingredient at the inflammation site and exhibits a local effect.
The direct use of the active ingredient following the grinding up by pestle and mortar of capsules resistant to gastric juice to treat GVHD (Elad, 2003) is known. This direct use of the active ingredient mentioned in the prior art suffers from various disadvantages, for example of not being a ready-for-use, industrially producible formulation with a reproducible dosage. Grinding up tablets also has the disadvantage that uniform high concentrations of active ingredient are not provided at the inflammation site.
The specific tablet formulation is used for buccal administration, in particular with the objective of absorbing an active ingredient buccally into the systemic circulation. Wetting the entire region of the oral cavity with dissolved active ingredient for local use is not possible.
The high instability of budesonide in dissolved form rules out the production of a dissolved pharmaceutical preparation containing budesonide. Over an extended period of time, such a budesonide solution would not be stable without a precise pH adjustment and the addition of preservatives and further stabilisers.
An object of the present invention is to provide a pharmaceutical formulation which can be administered orally and which no longer suffers from the mentioned disadvantages.
Therefore, according to the invention, a formulation is provided which exhibits a rapid, improved solubility for budesonide when prepared as a mouth rinsing solution, results in a high local concentration of active ingredient and furthermore allows a safe use with few side effects over an extended period of time. In addition, the effervescent tablet according to the invention allows stable storage and simple handling.